Program in the chemoenzymatic synthesis of alkaloids and medicinal agents and the development of new chiral building blocks, asymmetric protocols, and reagents

生物碱和药剂的化学酶合成以及新的手性构件、不对称方案和试剂的开发项目

• 批准号: RGPIN-2018-03723
• 负责人: Hudlicky, Tomas
• 金额: $ 5.76万
• 依托单位: Brock University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=712523
• 关键词: Program; chemoenzymatic; synthesis; alkaloids; medicinal

Our research program is focused on developing efficient manufacturing protocols for important medicinal compounds by environmentally friendly methods (green chemistry). The key component of the program is biocatalysis (or biotransformations) where we use special organisms (or isolated enzymes) to perform some chemical reactions in aqueous medium. We use these tools to make useful substances in fewer steps by a safer process that produces less hazardous waste. Over the next five years our program will focus on the following: By means of biocatalysis, we will make new building blocks useful for other chemical reactions. We will also develop a new method for converting alkaloid components of the poppy plant to medicinally useful substances. Enzymes will be used to remove a methyl group from the nitrogen in the natural compounds, a process that is difficult to achieve by chemical methods. We will develop two new synthetic methods. (1) We will make carbasugars (structurally related to sugars, with a number of pharmaceutical applications) from some of the building blocks made by biocatalysis. (2) We will develop a short process for converting an ester to a methyl group. In the area of target-oriented synthesis, we will design and synthesize new derivatives of compounds naturally occurring in various plants in the amaryllis family and study their mode of action. Some that we have already made have anti-cancer properties. We will also embark on a new generation of syntheses of morphine-related substances, an area in which we have a lot of experience. Among other projects in our program, we will study the structureactivity relationship of pleiogenone, a substance with biological activity isolated from the bark of Burdekin plum trees and recently prepared. We will complete a formal total synthesis of tetrodotoxin, the potent neurotoxin from puffer fish, where we will make more efficiently a key intermediate used in another synthesis. We will use building blocks from our biocatalytic processes to make chiral polymers to use in materials and templates for catalysis. Another long-term goal is to design a catalyst as a chemical equivalent of the enzyme that is employed in our biocatalysis projects. Our research will contribute to the development of new replacement technology for traditional manufacturing of specialty chemicals and pharmaceutical agents through biological methods and the use of enzymes from bacteria, fungi, and plants. The research will provide excellent training for future chemistry professionals both in the pharmaceutical industry and in academia. The best means of training chemists is offered by projects in total synthesis where they are exposed to a full set of situations and challenges encountered in pharmaceutical industry. Collaborations that emerge during our research require team effort and meeting of timelines. Together, such training produces outstanding professionals.

我们的研究重点是通过环保方法（绿色化学）开发重要药物化合物的高效制造方案。该计划的关键组成部分是生物催化（或生物转化），我们使用特殊的生物体（或分离的酶）在水介质中进行一些化学反应。我们使用这些工具，通过更安全的过程，以更少的步骤制造有用的物质，产生更少的有害废物。